According to a nationwide government survey released in December 2008, approximately 38% of U.S. adults and approximately 12% of children use some form of complementary and alternative medicines (CAM) (information can be found on the World Wide Web at nccam.nih.gov/news/camstats/2007/camsurvey_fsl.htm). This study revealed that the use of many forms of CAM significantly increased in prevalence between 2002 and 2007. Although not specifically studied, the incidence of CAM use in oncology patients is likely even higher due to a desperate attempt of many cancer patients to find therapies that are believed to be more effective and less toxic than conventional medicines. This same time period has also seen large numbers of articles in the lay press extolling the benefits of these therapies thereby increasing awareness of them in the general population. Together, increased opportunity and increased awareness may explain much of the observed increase in adult use of CAM.
While the use of these therapies has increased, scientific research provided only limited evidence of clinical efficacy. For instance, the National Library of Medicine journal database, PubMed, identified 40 systematic reviews published between 2002 and 2007. Of these, only 10 (25%) of the systematic reviews found sufficient evidence to conclude that a given CAM therapy was effective for a given condition. While many believe that some of these therapies have significant therapeutic potential, there needs to be better, more rigorous scientific studies to back up the purported claims before they can be recommended for use (information can be found on the World Wide Web at nccam.nih.gov/news/camstats/2007/camsurvey_fsl.htm).
Growth inhibition of Ehrlich ascites tumor can be achieved by treatment of tumor-bearing mice with a mixture of 2,6-dimethoxy-p-benzoquinone-DMBQ and ascorbic acid (Pethig, R. et al., Proc. Natl. Acad. Sci. U.S.A. 80:129 (1983).). This mixture produces long-lived semiquinone and ascorbic free radicals. Vitamin C is present in many plants, while DMBQ is present in wheat germ. It has been shown that quenching of quinone and ascorbic radicals depends on an NADPH-dependent SH group containing enzyme (Pethig, R. et al., Proc. Natl. Acad. Sci. U.S.A. 81:2088 (1984).). The cytotoxicity of the radical mixture was supposed to be associated with the decreased NADP-reducing capacity of tumor cells (Pethig, R. et al., Proc. Natl. Acad. Sci. U.S.A. 82:1439 (1985).). During the fermentation of wheat germ, yeast quinones are released by the glycosidase enzyme of the yeast. It has been hypothesized that the biological activity of these released quinones relates to “immunostimulatory effects”. Based on this hypothesis studies by Szent-Györgyi, produced a dried standardized extract of wheat germ fermented by Saccharomyces cereiisiae. The fermentation process had previously been optimized to yield DMBQ in the extract. The dried extract was named MSC (Trade name: AVEMAR) (Pethig, R. et al., Proc. Natl. Acad. Sci. U.S.A. 80:129 (1983); and Zalatnai, et al., Carcinogenesis, 22(10):1649-1652 (2001)). The final product, Avemar pulvis, comprises 63.2% fermented wheat germ, 35.0% maltodextrin, and 1.8% colloidal silicon dioxide. The product has been reported to be standardized to the DMBQ content (Tomoskozi-Farkas and Daood, 2004; Fajka-Boja, Int J. Oncol. 2002 (3):563-70). Flavors and sweeteners, including fructose, natural orange flavor and sodium chloride have been added to Avemar pulvis and the product sold under trade name, Ave', in the United States (American Biosciences, Inc. Blauvelt, N.Y.).
Preliminary in vitro studies with MSC have demonstrated induction of apoptosis and necrosis in pancreatic carcinoma cells, T lymphocytic tumor cell lines, and leukemia cells in vitro (Boros L G et al., Pancreas 23:141-147 (2001); Comin-Anduix B et al., J Biol Chem 277:46408-46414 (2002); and Fajka-Boja R et al., Int J Oncol 20:563-570 (2002)). In T lymphoid tumor cells, apoptosis was selectively induced via tyrosine phosphorylation and calcium influx (Fajka-Boja R et al., Int J Oncol 20:563-570 (2002).). In addition, MSC was shown to have a selective inhibitory effect on glycolysis and pentose cycle enzymes, and to cause the down-regulation of major histocompatibility complex class I proteins in tumor cells (Boros L G et al., Pancreas 23:141-147 (2001); Comin-Anduix B et al., J Biol Chem 277:46408-46414 (2002); and Fajka-Boja R et al., Int J Oncol 20:563-570 (2002)). Avemar treatment for 24 hrs caused necrosis in 28% and apoptosis in 22% of the cells. Avemar inhibited the cell-cycle progression of HT-29 colon cancer cells in the G1 phase of the cell cycle. In addition, Avemar inhibited the activity of the key enzyme of de novo DNA synthesis, ribonucleotide reductase. In addition, Avemar inhibited the activity of cyclooxygenase-1 and -2. Although no chemical constituents are yet isolated and tested experimentally, it has been hypothesized that benzoquinones, wheat germ agglutinin (WGA), fiber, lipids and phytic acid in wheat bran play a role in exerting anti-carcinogenic effects. In a recent report utilizing intracellular carbon flow studies with a 13C-labeled isotope of glucose and biological mass spectrometry (GC/MS), it was demonstrated that fermented wheat germ inhibits nucleic acid ribose synthesis in a dose dependent fashion primarily through the non-oxidative steps of the pentose cycle while increasing direct glucose carbon oxidation and acetyl-CoA utilization toward fatty acid synthesis in pancreatic adenocarcinoma cells (information can be found on the World Wide Web at nccam.nih.gov/news/camstats/2007/camsurvey_fsl.htm). These metabolic changes indicate that FWGE exerts its anti-proliferative action through altering metabolic enzyme activities which primarily control glucose carbon flow toward nucleic acid synthesis.